Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

2 genetic variations predict second cancers after radiation for children with Hodgkin lymphoma

25.07.2011
A genome-wide association study published in the August issue of Nature Medicine has found two tiny genetic variations that can predict which patients with Hodgkin's lymphoma are most likely to develop radiation-induced second cancers years after treatment. Knowing in advance who is at risk could help physicians tailor treatment to reduce the risks for patients who are most susceptible to long-term damage.

Hodgkin's lymphoma is one of the most treatable cancers, with more than 90 percent of patients surviving after a combination of radiation and chemotherapy. But nearly 20 percent of patients treated as children develop a second cancer within 30 years. The younger the patients are when treated and the higher the radiation dose, the greater the risk. This late side effect of treatment is the second leading cause of death for long-term Hodgkin's survivors.

"This finding means we can better identify children who are most susceptible to radiation-induced cancers before treatment begins and modify their care to prevent this serious long-term complication," said Kenan Onel, MD, PhD, associate professor of pediatrics and senior author of the study. "Luckily our options for Hodgkin's are broad enough that we can find ways to control the initial disease without relying on radiation therapy."

"This is also a triumph for genome-wide association studies," he added. "Many previous GWAS studies found multiple genetic differences, with each of them playing only a modest role, with minimal impact on clinical management. In this study, which focused on the interaction between genes and a very specific environmental factor—cancer long after radiation therapy—a small number of genetic differences produced a very big impact."

Onel and colleagues analyzed the genomes of 178 Hodgkin's patients who had been treated between the ages of 8 and 20 with chemotherapy and radiation therapy. Within 30 years after treatment, 96 of them had developed second cancers and 82 had not.

When they scanned each patient's genome, focusing on 665,313 tiny genetic variations known as single nucleotide polymorphisms, they found three variations that appeared far more often in patients with second cancers. When they repeated the study using a different set of patients—62 cases with second cancers and 71 without—two of the three markers were significant.

Those two markers were both from a small region known as 21q on chromosome 6. Both are positioned near a gene known as PRDM1.

The genetic variations closely associated with increased cancer risk, and with each other, appeared to decrease activation of the PRMD1 gene. They had no detectable effect any other genes. Cells with the protective version of both markers expressed PRDM1 after being exposed to radiation. Cells with the variants linked to subsequent cancers did not produce any PRDM1.

Previous studies have found that PRDM1 is involved in a variety of fundamental cellular processes, including proliferation, differentiation and apoptosis—which can all go awry in cancer. The gene's activity is lost in many cancer types.

In Onel's small samples, only three percent of patients with both of the protective variants developed second cancers within 30 years; nearly 33 percent of those with both of the high-risk variations did.

"Taken together," the authors note, "our findings support a novel role for PRDM1 as a radiation-responsive tumor suppressor." PRMD1 may be important for understanding the causes of second cancers in survivors of pediatric Hodgkin's lymphoma as well as in other cancer patients treated with radiation therapy."

This study should also "bring some optimism" back to genome-wide association studies, Onel added. Most previous cancer-related markers found through GWAS have been "of little clinical value for predicting risk, response to therapy or survival." But by incorporating environmental exposure, such as radiation therapy, into genomic investigations, "much of the missing heritability can be revealed," he said. "By folding in the environmental component, we were able to ask a more targeted question. This approach could improve our ability to integrate genomics into routine cancer care."

The National Institutes of Health, the American Cancer Society, American Lebanese Syrian Associated Charities, the Leukemia Lymphoma Society, the Breast Cancer Research Foundation, the Cancer Research Foundation, and the University of Chicago Comprehensive Cancer Center supported this research.

Additional authors include Timothy Best, Andrew Skol, Sarah Jackson, Olufunmilayo Olopade and Stephanie Huang of the University of Chicago; Dalin Li, Thomas Mack, Wendy Cozen and David Conti of University of Southern California; Kenneth Offit and Thomas Kirchhoff of Memorial Sloan Kettering Cancer Center; Yutaka Yasui of the University of Alberta; Smita Bhatia of City of Hope; Louise Strong of the MD Anderson Cancer Center; Susan Domchek and Katherine Nathanson of the University of Pennsylvania; and Leslie Robison of St Jude Children's Research Hospital.

John Easton | EurekAlert!
Further information:
http://www.uchospitals.edu

More articles from Life Sciences:

nachricht New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center

nachricht Exposure to fracking chemicals and wastewater spurs fat cell development
22.06.2018 | Duke University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

New cellular pathway helps explain how inflammation leads to artery disease

22.06.2018 | Life Sciences

When fluid flows almost as fast as light -- with quantum rotation

22.06.2018 | Physics and Astronomy

Exposure to fracking chemicals and wastewater spurs fat cell development

22.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>